Correlation Between Renal Biomarkers, Glomerular Filtration Rate, and Meropenem Clearance in Pediatric Septic Shock

The primary objectives were to identify the correlation between various estimated glomerular filtration rate (eGFR) methods and observed meropenem clearance (CL_MERO) in hospitalized children on meropenem and to identify patients with acute kidney injury (AKI) or augmented renal clearance (ARC).

We prospectively assessed children aged 4 weeks to 21 years who received meropenem 20mg/kg IV every 8 hours from 2019 to 2023. Cases with sepsis were compared with controls without sepsis. Plasma meropenem concentrations and renal function biomarkers (serum creatinine [SCr], cystatin C [SCys]) were measured. GFR was estimated using: eGFR-MS (modified Schwartz for <18 years old and CKD-EPI for ≥ 18 years old), 3 equations by Pierce using SCr (eGFR-Cr) or SCys (eGFR-Cys) or their average (eGFR-Avg), and eGFR-Pot (Pottel).

Analysis included 27 subjects (n = 19 cases and n = 8 controls) with 309 meropenem serum concentrations. Median age was 11.8 (range 0.6-19.6) years, weight 36.3 (7.2-98.0) kg, CL_MERO 122.7 (35.7-422.3), eGFR-MS 138.9 (22.9-364.8), eGFR-Cr 122.1 (24.0-601.8), eGFR-Cys 163.0 (47.5-432.4), eGFR-Avg 143.06 (35.75-395.7), and eGFR-Pot 138.92 (25.98-614.09) mL/min/1.73 m². The correlation between all eGFR methods to CL_MERO was weak (Spearman Rho ranged from 0.073 to 0.14). SCr-based eGFR and SCys-based eGFR had a discordance in identifying ARC and AKI in 41% of patients.

The renal function of critically ill children, especially with sepsis, was extremely diverse and variable by day. Current eGFR methods had weak correlation to CL_MERO.